Advancement and Applications of Nanotherapy for Cancer Immune Microenvironment

Cancer treatment has evolved rapidly due to major advances in tumor immunity research.However,due to the complexity,heterogeneity,and immunosuppressive microenvir-onment of tumors,the overall efficacy of immunotherapy is only 20%.In recent years,nanoparticles have attracted more attention in the field of cancer immunotherapy because of their remarkable advantages in biocompatibility,precise targeting,and controlled drug delivery.However,the clinical application of nanomedicine also faces many problems concerning biological safety,and the synergistic mechanism of nano-drugs with immunity remains to be elucidated.Our study summarizes the functional characteristics and regulatory mechanisms of nanoparticles in the cancer immune microenvironment and how nanoparticles activate and long-term stimulate innate immunity and adaptive immunity.Finally,the current problems and future development trends regarding the application of nanoparticles are fully discussed and prospected to promote the transformation and application of nanomedicine used in cancer treatment.

Bioinformatic and Experimental Analyses Reveal That KIF4A Is a Biomarker of Therapeutic Sensitivity and Predicts Prognosis in Cervical Cancer Patients

Objective This study aims to investigate the expression,prognostic value,and function of kinesin superfamily 4A(KIF4A)in cervical cancer.Methods Cervical cancer cell lines(Hela and SiHa)and TCGA data were used for experimental and bioinformatic analyses.Overall survival(OS)and progression free survival(PFS)were compared between patients with high or low KIF4A expression.Copy number variation(CNV)and somatic mutations of patients were visualized and GISTIC 2.0 was used to identify significantly altered sites.The function of KIF4A was also explored based on transcriptome analysis and validated by experimental methods.Chemotherapeutic and immunotherapeutic benefits were inferred using multiple reference databases and algorithms.Results Patients with high KIF4A expression had better OS and PFS.KIF4A could inhibit proliferation and migration and induce G1 arrest of cervical cancer cells.Higher CNV load was observed in patients with low KIF4A expression,while the group with low KIF4A expression displayed more significantly altered sites.A total of 13 genes were found to mutate more in the low KIF4A expression group,including NOTCH1 and PUM1.The analysis revealed that low KIF4A expression may indicate an immune escape phenotype,and patients in this group may benefit more from immunotherapy.With respect to chemotherapy,cisplatin and gemcitabine may respond better in patients with high KIF4A expression,while 5-fluorouracil etc.may be responded better in patients with low KIF4A expression Conclusion KIF4A is a tumor suppressor gene in cervical cancer,and it can be used as a prognostic and therapeutic biomarker in cervical cancer.

Sports Injury-Related Fingers and Thumb Deformity Due to Tendon or Ligament Rupture

Background：Hand injuries are very common in sports,such as skiing and ball sports.One of the major reasons causing hand and finger deformity is due to ligament and tendon injury.The aim of this study was to investigate if the high-resolution 3T magnetic resonance imaging （MRI） can demonstrate the complex anatomy of the fingers and thumb,especially the tendons and ligaments,and provide the accurate diagnosis of clinically important fingers and thumbs deformity due to ligamentous and tendinous injuries during sport activities.Methods：Sixteen fresh un-embalmed cadaveric hands were harvested from eight cadavers.A total of 20 healthy volunteers＇ hands and 44 patients with fingers or thumb deformity due to sports-related injuries were included in this study.All subjects had MR examination with T1-weighted images and proton density-weighted imaging with fat suppression （PD FS） in axial,coronal,and sagittal plane,respectively.Subsequently,all 16 cadaveric hands were sliced into 2-mm thick slab with a band saw （six in coronal plane,six in sagittal plane,and four in axial plane）.The correlation of anatomic sections and the MRI characteristics of tendons of fingers and the ulnar collateral ligament （UCL） at the metacarpal phalangeal joint （MCPJ） of thumb between 20 healthy volunteers and 44 patients （confirmed by surgery） were analyzed.Results：The normal ligaments and tendons in 16 cadaveric hands and 20 volunteers＇ hands showed uniform low-signal intensity on all the sequences of the MRI.Among 44 patients with tendinous and ligamentous injuries in the fingers or thumb,12 cases with UCL injury at MCPJ of the thumb （Stener lesion =8 and non-Stener lesion=4）,6 cases with the central slip injury,12 cases with terminal tendon injury,and 14 cases with flexor digitorum profundus injury.The ligaments and tendons disruption manifested as increased signal intensity and poor definition,discontinuity,and heterogeneous signal intensity of the involved ligaments and tendons.Conclusions：Sports injury-related fingers and thumb deformity are relatively common.MRI is an accurate method for evaluation of the anatomy and pathologic conditions of the fingers and thumb.It is a useful tool for accurate diagnosis of the sports-related ligaments and tendons injuries in hand.

Research on temperature field of non-uniform heat source model in surface grinding by cup wheel

To address the problems of thermal damage to a workpiece surface caused by the instantaneous high temperature during grinding and the difficulty in monitoring temperature in real time,the temperature field in the case of composite surface grinding by a cup wheel is studied.In order to predict the grinding temperature,considering material removal and grinding force distribution,a nonuniform heat source model with different function distributions in the circumferential and radial directions in the cylindrical coordinate system is first proposed;then,the analytical model is deduced and the numerical model of the temperature field is established based on the heat source model.The validation experiments for grinding temperature field are carried out using a high-definition infrared thermal imager and an artificial thermocouple.Compared to the temperature field based on the uniform heat source model,the results based on the non-uniform heat source model are in better agreement with the actual temperature field,and the temperature prediction error is reduced from approximately 23% to 6%.Thus,the present study provides a more accurate theoretical basis for preventing bums in cup wheel surface grinding.